Initial studies of immune checkpoint inhibitors in biomarker unselected gastro-oesophageal cancer yielded limited improvement in survival. However, emerging data from recent clinical trials suggest immunotherapies may offer a meaningful clinical benefit within selected populations. Gastro-oesophageal cancer is a heterogeneous disease with respect to histopathological and molecular features; hypermutation and the biology of immune checkpoint pathways are key to appropriate selection of populations most likely to benefit from immune checkpoint inhibitors. Programmed death-ligand 1 expression, typically measured using the combined positive score, is an important biomarker in determining which patients may benefit from immunotherapy agents. However, combined positive score thresholds are not standardised across trials and the benefit in programmed death-ligand 1-negative cohorts is uncertain. Data suggest that patients with tumours with microsatellite instability, high tumour mutational burden and Epstein-Barr Virus positivity are more likely to benefit from immunotherapy, which may be of importance within programmed death-ligand 1-negative populations. Here, we describe the current evidence base for the use of checkpoint inhibitors in the treatment of advanced gastro-oesophageal cancer and adjuvant treatment of high-risk oesophageal cancer, as well as the ongoing studies of immunotherapy in the treatment of patients with gastro-oesophageal cancers across an increasing range of clinical settings.

中文翻译：

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胃食管癌的免疫治疗：个性化治疗的当前实践和未来。

免疫检查点抑制剂在生物标志物未选择的胃食管癌中的初步研究对生存率的改善有限。然而，最近临床试验的新数据表明，免疫疗法可能会在特定人群中提供有意义的临床益处。就组织病理学和分子特征而言，胃食管癌是一种异质性疾病。超突变和免疫检查点途径的生物学是最有可能受益于免疫检查点抑制剂的适当人群的关键。程序性死亡配体 1 表达，通常使用联合阳性评分来衡量，是确定哪些患者可能受益于免疫治疗药物的重要生物标志物。然而，综合阳性评分阈值在试验中未标准化，程序性死亡配体 1 阴性队列的益处不确定。数据表明，具有微卫星不稳定性、高肿瘤突变负荷和 Epstein-Barr 病毒阳性的肿瘤患者更有可能从免疫治疗中受益，这在程序性死亡配体 1 阴性人群中可能很重要。在这里，我们描述了目前使用检查点抑制剂治疗晚期胃食管癌和辅助治疗高危食管癌的证据基础，以及正在进行的免疫疗法治疗胃食管癌患者的研究。癌症在越来越多的临床环境中。数据表明，具有微卫星不稳定性、高肿瘤突变负荷和 Epstein-Barr 病毒阳性的肿瘤患者更有可能从免疫治疗中受益，这在程序性死亡配体 1 阴性人群中可能很重要。在这里，我们描述了目前使用检查点抑制剂治疗晚期胃食管癌和辅助治疗高危食管癌的证据基础，以及正在进行的免疫疗法治疗胃食管癌患者的研究。癌症在越来越多的临床环境中。数据表明，具有微卫星不稳定性、高肿瘤突变负荷和 Epstein-Barr 病毒阳性的肿瘤患者更有可能从免疫治疗中受益，这在程序性死亡配体 1 阴性人群中可能很重要。在这里，我们描述了目前使用检查点抑制剂治疗晚期胃食管癌和辅助治疗高危食管癌的证据基础，以及正在进行的免疫疗法治疗胃食管癌患者的研究。癌症在越来越多的临床环境中。